University of California, Department of Molecular and Cell Biology, Cancer Research Laboratory Berkeley , Berkeley, CA 94720-3200 , USA.
Expert Opin Biol Ther. 2014 Jul;14(7):947-54. doi: 10.1517/14712598.2014.900540. Epub 2014 Mar 24.
INTRODUCTION: Chimeric antigen (or antibody) receptors (CAR) are fusion proteins typically combining an antibody-derived targeting fragment with signaling domains capable of activating immune cells. Recent clinical trials have shown the tremendous potential of adoptive cell transfer (ACT) of autologous T cells engineered to express a CD19-specific CAR targeting B-cell malignancies. Building on this approach, ACT therapies employing allogeneic CAR-expressing cytotoxic cells are now being explored. AREAS COVERED: The basic principles of CAR-ACT are introduced. The potential benefits as well as problems of using allogeneic CAR-modified cells against tumor antigens are discussed. Various approaches to allogeneic CAR therapy are presented, including donor leukocyte infusion, CAR-redirected γδ T cells and natural killer cells, strategies to avoid graft-versus-host disease, modulation of lymphocyte migration, and exploitation of graft-versus-host reactivity. EXPERT OPINION: CAR-modified allogeneic cells have the potential to act as universal effector cells, which can be administered to any patient regardless of MHC type. Such universal effector cells could be used as an 'off-the-shelf' cell-mediated treatment for cancer.
简介:嵌合抗原(或抗体)受体(CAR)是一种融合蛋白,通常将抗体衍生的靶向片段与能够激活免疫细胞的信号结构域结合在一起。最近的临床试验表明,对表达针对 B 细胞恶性肿瘤的 CD19 特异性 CAR 的自体 T 细胞进行过继细胞转移(ACT)具有巨大的潜力。在此基础上,现在正在探索使用同种异体表达 CAR 的细胞毒性细胞的 ACT 疗法。
涵盖的领域:介绍了 CAR-ACT 的基本原理。讨论了使用针对肿瘤抗原的同种异体 CAR 修饰细胞的潜在益处和问题。提出了各种同种异体 CAR 治疗方法,包括供体白细胞输注、CAR 重定向的 γδ T 细胞和自然杀伤细胞、避免移植物抗宿主病的策略、淋巴细胞迁移的调节以及利用移植物抗宿主反应。
专家意见:CAR 修饰的同种异体细胞有可能作为通用效应细胞,可用于任何患者,而与 MHC 类型无关。这种通用效应细胞可作为癌症的“现成”细胞介导治疗方法。
Expert Opin Biol Ther. 2014-3-24
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